The present invention relates to biodegradable hyaluronic acid filler compositions for soft tissue implants and body augmentation such as dermal fillers or breast, butt or body implants.
Everyone wants healthy and younger-looking skin. Having smooth skin and youthful appearance can make a person appear years younger, feel beautiful and more self-assured. Injectable dermal implants are a popular solution to correct a wide variety of facial contour defects that are congenital or as a result of serious accidents. The injectable dermal implants are very effective in cosmetic surgery procedures such as lip augmentation and scar removal.
Generally, as the years take its tolls on the body, the cells that generate the connective tissues that makeup the scaffold of the body become less efficient, and cannot keep up with the daily repair processes. Thus, our skin loses resiliency, elasticity and from which onsets wrinkles. The gerontological process happens at seemingly exponential speed.
The concept of biocompatibility is moving from a “do-no-harm” mission (i.e., nontoxic, non-antigenic, non-mutagenic, etc.) to one of “doing-good,” that is, encouraging positive healing responses. These new devices will promote the formation of normal healthy tissue as well as the integration of the device into adjacent tissue. In some contexts, biocompatibility can become a disruptive technology that can change therapeutic paradigms (e.g., drug-coated stents).
The required material properties are determined by the specific device application and the functional life of the device, which ranges from temporary use to permanent implant. Devices can be used in:
1. blood-contacting applications such as extracorporeal devices that remove and return blood from the body, devices that are inserted into a blood vessel, or devices that are permanently implanted.
2. soft-tissue device applications, such as soft-tissue augmentation;
3. orthopedic and dental applications for joint, bone, and tooth replacement and repair
4. specific organ applications (e.g., neural); and
5. scaffolds for tissue engineering for tissue and organ replacement.
Development of an injectable hydrogel for tissue repair or tissue regeneration presents considerable challenges. The gelation conditions for in vivo use are limited to a narrow range of physiologically acceptable temperatures, and the crosslinking must occur with no by-products in a sensitive aqueous environment. Reagents must be nontoxic reagents and tolerant of moist, oxygen-rich environments. Furthermore, gelation must occur at a sufficiently rapid rate for clinical use in an outpatient or operating suite setting, yet sufficiently slow that complete mixing occurs prior to gelation.
In a parallel trend, millions of women have undergone breast, butt or body augmentation and reconstruction in the past few decades. Most women choose augmentation to enhance the size and shape of one or both breast, butt or body parts for personal or aesthetic reasons. In contrast, women who undergo a reconstruction procedure want to reconstruct a breast, butt or body that has been removed, typically for health reasons, such as tumor removal. The reconstruction procedure may vary from a modified radical mastectomy (removal of the underlying muscle as well as the breast, butt or body), to a simple mastectomy (removal of one breast, butt or body), to a bilateral mastectomy (removal of breast, butt or body parts) or to a lumpectomy (removal of a portion of the breast, butt or body). In either augmentation or reconstruction, the modality intimates the surgical implantation of breast, butt or body prosthesis (implant).
Conventional implants for treating breast, butt or body augmentation or reconstruction include a shell or envelope that is filled with a filler composition, for example, silicone gel, saline solution, or other suitable filler. It is desirable that the filler have lubricating properties to prevent shell abrasion, remain stable over long periods of time, be non-carcinogenic and non-toxic, and have physical properties to prevent skin wrinkling, capsular contracture formation, and implant palpability.
While breast, butt or body implants containing silicone-gel as a filler are widely used for breast, butt or body augmentation or reconstruction, a variety of potential disadvantages have been recognized with respect to the stabilization of the implants and the immune system. First, the silicone gel-filled implants have a tendency to leak. In 1992, the FDA issued a voluntary moratorium on silicone gel-filled implants due to public health concerns regarding the potential link between leaking silicone gel-filled implants and autoimmune diseases. To date, the long term effect of silicone-gel on the immune system is still unknown. Second, the leaking of the implants necessitates the need for additional surgeries for removal or repair of the implants. Third, the silicone-gel as a filling material has a greater density than saline or natural tissues which may cause recipients back pain. Fourth, silicone is a permanent filler composition and when it leaks, it can travel though out the body and can cause unwanted hard nodular formations if left untreated. Lastly, the silicone-gel implant although currently the state of the art, it does not mimic the touch and feel of a real breast, butt or body. It offers a more realistic feel than saline as a filler material.
Many plastic surgeons turned to saline as an alternative replacement for silicone-gel. Several implants which use saline are known and were found to be advantageous over silicone-gel for several reasons. Saline has a lower density than silicone-gel causing less strain on recipients' backs. In addition, if the implant leaks, the saline solution is biocompatible providing a more tolerated and safer implant than those containing silicone-gel.
However, while the saline implant offer significant advantages over the silicone-gel implant, various problems have been encountered. Implants using saline are disadvantageous in that they frequently result in capsular contraction, a phenomenon where the body forms a lining of fibrous tissue encapsulating the breast, butt or body implant and the resulting capsule tightens and squeezes the implant. Symptoms range from mild firmness and mild discomfort to severe pain, distorted shape, palpability of the implant, and/or movement of the implant. Additional surgery may be needed in cases where pain and/or firmness are severe. This surgery ranges from removal of the implant capsule tissue to removal and possibly replacement of the implant itself. There is no guarantee that capsular contracture will not occur after these additional surgeries.
Saline implants may have to be removed and replaced periodically for other reasons—they fracture or they deflate. Saline, because it is less viscous than silicone-gel, settles in the bottom portion of the implant when the recipient is upright. This leaves the upper portion of the implant prone to excessive folding or wrinkling, causing stress fracturing of the shell at the fold points. Furthermore, the saline-filled implants have a tendency to drain gradually in about ten years. Barring any deflation or rupture complications, saline as a filler for breast, butt or body implants produces an unnatural feel and look to the implant.
U.S. Pat. No. 6,881,226 discloses a breast, butt or body implant having at least an outer shell which is composed of a resorbable material. The implant, which can be formed entirely of bioresorbable material such as collagen foam, is sized and shaped to replace excised tissue. The implant supports surrounding tissue upon implantation, while allowing for in-growth of fibrous tissue to replace the implant. According to various alternative embodiments, the implant is elastically compressible, or can be formed from self-expanding foam or sponges, and can be implanted through a cannula or by injection, as well as by open procedures. The implant can carry therapeutic and diagnostic substances.
In response to the failures of saline and silicone-gel implants, there have been a number of attempts to make a prosthesis filled with a non-toxic filler that that mimics the shape and feel of a natural breast, butt or body provided by silicone-gel yet is safe to the immune system like saline. Other attempts to provide a safe filler material include polyethylene glycol. However, the triglyceride oil or honey fails to provide an implant that is aesthetically pleasing and also duplicates the touch and feel of a natural breast, butt or body due to the low viscosity of the fillers. Due to the limited options and the inadequacy of current fillers to achieve the desired results, there is a need for safe and efficacious fillers.